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Article Abstract
Purpose: The ClinGen Actionability Working Group (AWG) developed an evidence-based framework to generate actionability reports and scores of gene-condition pairs in the context of secondary findings from genome sequencing. Here we describe the expansion of the framework to include actionability assertions.
Methods: Initial development of the actionability rubric was based on previously scored adult gene-condition pairs and individual expert evaluation. Rubric refinement was iterative and based on evaluation, feedback, and discussion. The final rubric was pragmatically evaluated via integration into actionability assessments for 27 gene-condition pairs.
Results: The resulting rubric has a 4-point scale (limited, moderate, strong, and definitive) and uses the highest-scoring outcome-intervention pair of each gene-condition pair to generate a preliminary assertion. During AWG discussions, predefined criteria and factors guide discussion to produce a consensus assertion for a gene-condition pair, which may differ from the preliminary assertion. The AWG has retrospectively generated assertions for all previously scored gene-condition pairs and are prospectively asserting on gene-condition pairs under assessment, having completed over 170 adult and 188 pediatric gene-condition pairs.
Conclusion: The AWG expanded its framework to provide actionability assertions to enhance the clinical value of their resources and increase their utility as decision aids regarding return of secondary findings.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11298308 | PMC |
| http://dx.doi.org/10.1016/j.gim.2024.101164 | DOI Listing |
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Article Synopsis
- - The ClinGen Actionability Working Group (AWG) created a framework to evaluate and score gene-condition pairs related to secondary findings from genome sequencing, and recently added actionability assertions to this framework.
- - The initial rubric was based on previously evaluated pairs, refined through expert feedback, and now uses a 4-point scale to determine the actionability of each gene-condition pair, generating both preliminary and consensus assertions.
- - Over 170 adult and 188 pediatric gene-condition pairs have been assessed, with the aim of improving clinical decision-making regarding the return of secondary findings from genetic testing.
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